Phase 1/1b Trial of Donor γδ T--Cell Infusion for Treatment of Patients With Acute Myeloid Leukemia at High Risk of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
The purposes of the study are to determine the maximum tolerated dose (MTD) and effectiveness of Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion after an allogeneic hematopoietic cell transplant (alloHCT) to treat patients with Acute Myeloid Leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged between 18 and 75 years of age undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) or the treatment ELN 2017 adverse risk AML
- •Have < 5% blasts in bone marrow by morphology at the time of transplantation. Patients with pre-alloHCT or post-alloHCT flow cytometric or molecular evidence of MRD are allowed
- •Karnofsky performance status (KPS) ≥ 70% during the study screening.
- •Free of symptomatic congestive heart failure or uncontrolled arrhythmia
- •Adequate organ function as defined per protocol
- •Negative serum pregnancy test
- •Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for at least 30 days following study treatment (T-cell infusion); should a woman subject or female partner of a male subject become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Agreement to adhere to Lifestyle Considerations throughout study duration
排除标准
- •Current use of concomitant systemic glucocorticoid at the time of γδ T-cell infusion for any reason will not be allowed in order to avoid their immunosuppressive effects on γδ T-cell function.
- •Active grade II-IV acute GVHD (patients with prior GVHD should be off prednisone for at least 14 days prior to infusion of the study cell product).
- •Uncontrolled serious infection.
- •Morphologic relapse of leukemia at any timepoint after HCT.
- •Active central nervous system malignancy.
- •Pregnancy or lactation.
- •Treatment with another investigational drug or other intervention within 14 days of T-cell infusion
研究组 & 干预措施
Dose Level -1
Dose Level -1 may be used as a de-escalation dose level due to Dose Limiting Toxicities (DLTs) from Dose Level 1
Participants will receive 1.0 x 106 cells/kg (0.75-1.25 x 106 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion
干预措施: Gamma Delta T-Cell Infusion (Biological)
Dose Level 1
Participants will receive 5.0 x 106 cells/kg (3.75-6.25 x 106 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion
干预措施: Gamma Delta T-Cell Infusion (Biological)
Dose Level 2
Participants will receive 2.5 x 107 cells/kg (1.875-3.125 x 107 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion
干预措施: Gamma Delta T-Cell Infusion (Biological)
Dose Level 3
Participants will receive 1.0 x 108 cells/kg (0.75-1.25 x 108 cells/kg) Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells administered as a single infusion
干预措施: Gamma Delta T-Cell Infusion (Biological)
Treatment at Maximum Tolerated Dose
Participants will receive Artificial Antigen Presenting Cell (AAPC)-expanded donor T-cells at the dose determined to be the Maximum Tolerated Dose, administered as a single infusion
干预措施: Gamma Delta T-Cell Infusion (Biological)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: Up to 12 months
Maximum Tolerated Dose will be determined by testing increasing doses of AAPC-expanded donor γδ T-cells.
Dose Expansion: Leukemia Free Survival
时间窗: Up to 12 months
Leukemia-free survival is defined as the time from the date of start of treatment to the date of relapse of AML or death from any cause
次要结局
- Number of Participants with Graft Versus Host Disease (GVHD)(at 6 weeks)
- Overall Survival (OS)(Up to 12 months)